JP2012515211A - Methods for improving liver and immune function in animals - Google Patents

Abstract

The present invention includes compositions and methods for improving animal health, and in certain embodiments, compositions and methods for improving liver and immune function in aged felines.
[Selection] Figure 1

Description

Cross-reference to related applications
[001] This application is a continuation-in-part of pending application serial number 11 / 753,404 filed May 24, 2007, which is a PCT application number filed November 23, 2005. PCT / US05 / 42886, which claims the benefit of provisional application serial number 60/630971, filed November 24, 2004.

  [0002] The present invention includes compositions and methods for improving animal health, and in certain embodiments, compositions and methods for improving liver and immune function in aged feline animals.

  [0003] The liver is an organ necessary for the maintenance of life and has an important role in almost all bodily functions of mammals. In one role, the liver acts as a filtration system to protect other organs from the effects of toxin accumulation. Toxins absorbed from the digestive system are removed from the blood by the liver before they can affect the rest of the body. The ability of xenobiotics such as drugs, therapeutic agents, or chemicals to cause damage to the liver is known as liver toxicity. Xenobiotics are pharmacologically or toxicologically active substances that are not produced inbornly and are therefore foreign to the body. Many industrial compounds, drugs and other therapeutic agents are well established to be damaging to the liver. As mammals age, their ability to filter and clear xenobiotics by the liver decreases. It is well known that as mammals, especially companion animals, age, they face health problems that require drugs and other therapeutic agents. Because liver filtration and clearance is reduced in such aging animals, administration of such drugs and therapeutic agents to improve the health of the animals may have a hepatotoxic effect.

  [0004] R-α-lipoic acid (CAS number 200-22-2, also known as thioctic acid and 1,2-dithiolane-3-pentanoic acid) occurs naturally in plant and animal tissues where it is lysine It is covalently bound to the ε-amino group of the residue. Lipoic acid is commercially available and is produced by companies such as BASF and Cognis. Lipoic acid is commercially available as essentially pure R-α lipoic acid or as a racemic mixture of lipoic acid isomers. In plants, lipoic acid is most abundant in spinach and potatoes, while in animal tissues, lipoic acid is most abundant in the kidney and heart. R-α-lipoic acid was first discovered in 1937 (see Snell et al., Journal Bact. 33; 207, 1937) and was not isolated and characterized until 1951 (Reed et al. Science 114: 94-4, 1951). R-α-lipoic acid can be synthesized and the methods are well known in the art. (See U.S. Pat. No. 2,890,716 to Reed, issued April 18, 1961). R-α lipoic acid has been classified as an antioxidant and has been used in high doses as a treatment for type II diabetes. Studies have shown that a mixture of carnitine and lipoic acid can enhance metabolism and relieve oxidative stress. (See US Pat. No. 5,916,912 to Ames et al. Issued June 29, 1999 and US Pat. No. 6,365,622 to Cavayoso issued April 2, 2002) . In addition, it has been shown that companion animal feeds that contain lipoic acid in combination with other ingredients appear to suppress the deterioration of mental ability of older companion animals. (See US Patent Application Publication Nos. 2002/0076469, 2002/0052402, 2002/0076470, 2000/115710, and 2002/0119182).

  [0005] Studies have shown that mitochondrial oxidation plays a role in lipoic acid metabolism. Its metabolism in humans is largely similar to that observed in mice and rats, but the formation of oxidized structures related to tetranorlipoic acid found in canines is not comparable in humans It seems. In addition, 3-ketripoic acid, an intermediate in the mitochondrial oxidation of lipoic acid, has been reported in plasma samples from rats and humans, but has not been found in plasma from canines. (See Schupke, H. et al. Drug Metabolism and Disposition, 29 (6) 855-862, 2001). The metabolic pathway of α-lipoic acid appears to be different in canines compared to humans.

  [0006] Mercapturic acid is a sulfur derivative of N-acetyl-cysteine, which is synthesized from glutathione (GSH). Most compounds that are metabolized to mercapturic acid generally first undergo conjugation with GSH catalyzed by an enzyme called glutathione S-transferase found in the soluble part of the liver refractions or in the supernatant. Accepted. The mercapturic acid pathway has evolved as a defense mechanism against xenobiotic-induced hepatotoxicity or carcinogenicity and serves to detoxify many harmful substances that are inhaled, ingested, or normally produced by daily metabolism Seems to play. Lipoic acid not only upregulates glutathione but also upregulates glutathione S-transferase, an enzyme that conjugated glutathione in the liver. Bromosulfphthalein (CAS No. 71-67-0, also known as BSP and sulfobromophthalein) is an organic dye, which, when infused into the circulation, removes many organic compounds in the liver. It is removed by the liver at a rate that reflects its ability to extract and metabolize. See S. M. Rosenthal, E.C. White, J. Pharmacol. 24, 265 (1924) W. Hacki et al., J. Lab. Clin. Med. 88, 1019 (1976). BSP is cleared from the liver in three stages. First, BSP is transferred from albumin through the plasma to the liver. This step depends on the plasma protein concentration and other ligands that bind to the plasma protein. BSP is then complexed by the ligand and z protein in the liver. Finally, BSP is conjugated with glutathione by the glutathione S-transferase enzyme and excreted into the bile duct, which is the rate limiting step. Thus, BSP is an example of a xenobiotic and provides information about the functional capacity of the liver when measured in blood after injection.

U.S. Pat. No. 2,890,716 US Pat. No. 5,916,912 US Pat. No. 6,365,622 US Patent Application Publication No. 2002/0076469 US Patent Application Publication No. 2002/0052402 US Patent Application Publication No. 2002/0076470 US Patent Application Publication No. 2000/115710 US Patent Application Publication No. 2002/0119182

Snell et al., Journal Bact. 33; 207, 1937 Reed et al. Science 114: 94-4, 1951 Schupke, H. et al. Drug Metabolism and Disposition, 29 (6) 855-862, 2001 S. M. Rosenthal, E.C. White, J. Pharmacol. 24, 265 (1924) W. Hacki et al., J. Lab. Clin. Med. 88, 1019 (1976)

[0007] The present invention generally includes a composition comprising an effective amount of lipoic acid or a salt thereof, wherein the effective amount is effective to improve liver or immune function in an animal.
[0008] In another aspect, the present invention provides a feed comprising lipoic acid or a salt thereof in an animal in need thereof, generally in an amount effective to improve liver function. Includes methods for improving liver function by giving in.

  [0009] In another aspect, the present invention provides a feed comprising lipoic acid or a salt thereof in an animal in need thereof, generally in an amount effective to improve immune function Includes methods for improving immune function by giving in.

  [0010] In various embodiments, the present invention is a novel approach to improve the health of aged animals, such as felines, for the use of lipoic acid or salts thereof as part of the feed provided to the animal. Based on use.

  [0011] Further areas of applicability of the present invention will become apparent from the detailed description provided below. It should be understood that the detailed description and specific examples, while indicating illustrative embodiments of the invention, are not intended to limit the scope of the invention.

[0012] FIG. 1 is a graphical representation that illustrates that inclusion of lipoic acid in a food at 65 ppm and 650 ppm for 6 weeks for cats had no adverse effects on body weight. [0013] FIG. 2 illustrates the effects on the content of 65 ppm and 650 ppm in the feed and the time of concanavalin A stimulation. There were no significant differences between groups at the start or end of the study. However, cats that ate 65 ppm lipoic acid content significantly increased the proliferation of lymphocytes activated by concanavalin A compared to baseline. Cats at 650 ppm also showed an increase. [0014] FIG. 3 illustrates that plant agglutinin (PHA) stimulation did not show significant differences between groups at the start or end. The explanatory group receiving 65 ppm lipoic acid had a significant increase in lymphocyte proliferation between baseline and 6 weeks of intervention. [0015] FIG. 4 illustrates that American pokeweed mitogen stimulation was different between groups at the start of the study (ANOVA P <0.05) but not at the end. The group with the lowest starting average was the 65 ppm group. Subsequently, lymphocyte proliferation in the group receiving 65 ppm lipoic acid increased significantly compared to baseline after a time of 6 weeks. [0016] Figures 5a and 5b illustrate the activity of natural killer cells. Based on an illustrative test, no significant change was detected from baseline to the end of the test for a 10: 1 stimulation ratio; however, all p values were less than 0.1. At a stimulation ratio of 50: 1, all changes between baseline and end of study were significant for all groups. [0016] Figures 5a and 5b illustrate the activity of natural killer cells. Based on an illustrative test, no significant change was detected from baseline to the end of the test for a 10: 1 stimulation ratio; however, all p values were less than 0.1. At a stimulation ratio of 50: 1, all changes between baseline and end of study were significant for all groups. [0017] FIG. 6 illustrates a graph for an exemplary Comet assay. Two illustrative assays were performed: (1) natural DNA damage and (2) damage loaded with hydrogen peroxide. Analysis of the data showed that all head DNA for all feeds increased significantly over the duration of the test for both (P <0.05). In addition, the tail length and olive tail moments of all tail DNAs decreased during the duration of the test for both the control and the hydrogen peroxide-loaded comet test. However, there was no significant difference between groups at either start or end for any of the comet measurements. In addition, ANOVA analysis of changes over time (pre-post-difference) showed no significant difference by t-test for each comet variation under control and hydrogen peroxide loading conditions.

  [0018] The figures are intended to illustrate the general features of the present invention for the description of such aspects herein. The figures may not accurately reflect the features of every given aspect and are not necessarily intended to define or limit specific aspects within the scope of the invention.

Definition
[0019] The term "animal" refers to any animal that is susceptible to or suffers from defective liver function and requires improved xenobiotic liver clearance, or from improved xenobiotic liver clearance. Means an animal that may benefit. An animal is “sensitive” to a disease or disorder if the animal shows signs that the animal is likely to develop the disease or disorder. An animal is “afflicted” of a disease or disorder if it exhibits symptoms that indicate that the animal has developed the disease or disorder.

  [0020] As used herein, the term "lipoic acid or salt thereof" includes, for example, alpha-lipoic acid, racemic mixtures of lipoic acids, lipoic acid salts, esters, amides or derivatives thereof such as US Pat. Examples include, but are not limited to, those described in 621,117. In various embodiments, the lipoic acid can be administered in a composition comprising a wet or dry food composition, which may be in the form of a wet food, dry food, supplement or treats. The lipoic acid may be incorporated therein or on the surface of any food composition, for example by spraying or sedimenting on it, or as a snack, supplement, treats in the feed or as a liquid part of the feed For example, it may be added in water or another liquid. The lipoic acid may be administered as a powder, a solid, or as a liquid containing a gel. An important aspect is that the animal is given an amount of lipoic acid effective to produce a positive effect. Typically, the source of lipoic acid or salt thereof is present in the composition in an amount up to an amount that remains non-toxic to the animal.

  [0021] The phrase "its salt" as used herein includes, but is not limited to, salts of lipoic acid used in pet food compositions. Lipoic acid is acidic in nature and can thus form base salts with various cations. Examples of such salts include alkali metal or alkaline earth metal salts and especially calcium, magnesium, sodium, lithium, zinc, potassium, and iron salts.

  [0022] The term "elderly animal" is any animal that is susceptible to or suffers from defective liver function due to age and requires improved xenobiotic liver clearance, or improved Means an animal that may benefit from liver clearance of xenobiotics.

General description
[0023] The present invention generally includes a composition comprising an effective amount of lipoic acid or a salt thereof, wherein the effective amount is effective to improve liver or immune function in an animal.

[0024] In certain embodiments, the effective amount is effective to improve liver function in an animal.
[0025] In other embodiments, the effective amount is effective to improve immune function in the animal.

[0026] In another embodiment, the effective amount is 25 ppm to 2600 ppm lipoic acid or a salt thereof.
[0027] In another embodiment, the effective amount is 50 ppm to 1200 ppm lipoic acid or a salt thereof.

[0028] In another embodiment, the effective amount is 65 ppm to 650 ppm lipoic acid or a salt thereof.
[0029] In another embodiment, the animal is a companion animal.

[0030] In another embodiment, the animal is a feline.
[0031] In another embodiment, the composition is a food composition.
[0032] In another embodiment, the food composition is suitable for companion animals.

[0033] In another embodiment, the food composition is extruded.
[0034] In another embodiment, the food composition is canned.
[0035] In another aspect, the invention includes a method for improving liver or immune function in an animal, comprising providing the animal with an effective amount of lipoic acid or a salt thereof, wherein The effective amount is effective to improve liver or immune function.

[0036] In certain embodiments, the method is effective to improve liver function in an animal.
[0037] In other embodiments, the method is effective to improve immune function in an animal.

[0038] In another embodiment, the effective amount is 25 ppm to 2600 ppm lipoic acid or a salt thereof.
[0039] In another embodiment, the effective amount is 50 ppm to 1200 ppm lipoic acid or salt thereof.

[0040] In another embodiment, the effective amount is from 65 ppm to 650 ppm lipoic acid or a salt thereof.
[0041] In another embodiment, the animal is a companion animal.

[0042] In another embodiment, the animal is a feline.
[0043] In another embodiment, the lipoic acid is part of the animal's daily diet.
[0044] In another embodiment, the daily feed comprises greater than 50 ppm lipoic acid based on dry weight.

[0045] In another embodiment, the lipoic acid is provided to the animal in a food composition suitable for consumption by the animal.
[0046] In another embodiment, the animal is an elderly animal.

[0047] Another embodiment includes a composition suitable for improving immune function in an animal comprising an amount of nutrients and greater than 50 ppm lipoic acid.
[0048] In certain embodiments, the composition is a food composition.

[0049] In other embodiments, the food composition is suitable for companion animals.
[0050] In another embodiment, the food composition is suitable for felines.
[0051] In another embodiment, the composition is extruded or canned.

Composition of the present invention
[0052] One embodiment of the present invention includes a composition for companion animals comprising an amount of lipoic acid or a salt thereof effective to improve liver or immune function in an animal.

  [0053] The amount of alpha-lipoic acid in the composition is from at least about 25 ppm to about 50 ppm, about 100 ppm, about 200 ppm, about 300 ppm, about 500 ppm, about 700 ppm, about 900 ppm, about 1100 ppm, about 1200 ppm, about 1400 ppm, It can vary from about 1600 ppm, about 1800 ppm, about 2000 ppm, about 2200 ppm, about 2400 ppm, or about 2600 ppm.

  [0054] In various embodiments, the range of lipoic acid that can be administered to a cat is 25 ppm to 2600 ppm. In certain illustrative aspects, the amount can vary from 65 ppm to an amount that remains non-toxic to the pet. In other embodiments, the range is 50 ppm to 1200 ppm. In other embodiments, the range is 65 ppm to 650 ppm.

  [0055] In various embodiments, a food composition comprising lipoic acid provides a substantially nutritionally complete feed to the intended recipient animal. A “nutritively complete feed” is a feed that contains enough nutrients to maintain the normal health of a healthy animal that eats the feed.

  [0056] The lipoic acid or salt thereof is present in a concentration that is not detrimental to the intended animal health. Thus, for example, the lipoic acid or salt thereof is present in a concentration that does not cause undesirable or toxic effects.

  [0057] The composition can be a liquid or solid hood. If the composition is a liquid, the lipoic acid or salt thereof can be mixed with other components. If the composition is a solid, the lipoic acid may be coated on the composition, incorporated into the composition, or both.

  [0058] In various embodiments, the lipoic acid or salt thereof may be added to animal food. In various embodiments, the lipoic acid or salt thereof may be added to the animal food, on site by the formulator or manufacturer, or by the animal caregiver prior to feeding the animal. In other embodiments, the lipoic acid or salt thereof may be added during processing of the animal food, for example during and / or after mixing of other components of the composition, which is then packaged and Will be available. The processing may include extrusion, canning, baking, and the like, or any other method or process for producing a pet food known in the art. In other embodiments, the lipoic acid or salt thereof may be contributed by a natural source such as an animal or plant component, or the lipoic acid or salt thereof may be contributed by a source derived from synthesis, or the lipoic acid thereof. The acid or salt thereof may be contributed by a mixture of natural and synthetic sources.

  [0059] The composition includes, in addition to lipoic acid or a salt thereof, at least one component suitable for consumption by companion animals, including fats, carbohydrates, proteins, fibers, nutritional balancing agents. ), Including but not limited to vitamins, minerals, and trace elements, and mixtures thereof. One skilled in the art will select the amount and type of food ingredients for a typical food based on the animal's dietary requirements, for example, based on the animal's species, age, size, weight, health, and function. Can do.

  [0060] The food ingredient portion of the food composition can include up to about 100% of any individual food ingredient, or can include mixtures at various ratios of food ingredients. In certain embodiments, the food composition comprises a combination of food ingredients in the following amounts: 0 wt% to 50 wt% fat, 0 wt% to 75 wt% carbohydrate, 0 wt% to 95 wt%. Protein, 0% to 40% dietary fiber, and 0% to 15% by weight of one or more nutritional regulators.

  [0061] In certain embodiments, the fat and carbohydrate food ingredients are obtained from a variety of sources such as animal fat, fish oil, vegetable oil, meat, meat by-products, cereals, other animal or plant sources, and mixtures thereof. Cereals include wheat, corn, barley, and rice.

  [0062] In certain embodiments, the protein food ingredient is obtained from a variety of sources, such as plants, animals, or both. Animal proteins include meat, meat by-products, milk-based, and eggs. Meat includes meat from poultry, fish, and animals such as cattle, pigs, sheep, goats, and the like, and meat by-products include lung, kidney, brain, liver, stomach, and intestine . The protein food ingredient may be free amino acids and / or peptides. Preferably, the protein food ingredient includes meat, meat by-products, dairy products, or eggs.

[0063] In certain embodiments, the fiber food ingredient is obtained from a variety of sources such as plant fiber sources such as cellulose, sugar beet pulp, peanut hulls and soy fiber.
[0064] In certain embodiments, the nutritional modifier is obtained from a variety of sources known to those skilled in the art, such as vitamins and mineral supplements and food ingredients. Vitamins and minerals can be included in amounts necessary to avoid deficiencies and maintain health. These quantities are readily available in the art. The National Research Council (NRC) provides recommended amounts of such nutrients for livestock. For example, Nutrient Requirements of Swine (10th revised edition, Nat'l Academy Press, Washington DC, 1998), Nutrient Requirements of Poultry (9th revised edition, Nat'l Academy Press, Washington DC, 1994), Nutrient Requirements of Horses (Fifth revised edition, Nat'l Academy Press, Washington DC, 1989). The American Diet Examiners Association (AAFCO) provides recommended amounts of such nutrients for dogs and cats. See the official publication of the American Feed Inspectors Association, pp. 129-137 (2004). Vitamins generally useful as food additives include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin D, biotin, vitamin K, folic acid, inositol, niacin, and pantothenic acid. Minerals and trace elements useful as food additives include calcium, phosphorus, sodium, potassium, magnesium, copper, zinc, chlorine, iron, selenium, iodine, and iron.

Preparation of the composition of the present invention
[0065] The compositions of the present invention may be prepared in canned or wet form using commonly used food preparation processes known to those skilled in the art. Typically, ground animal proteinaceous tissue is mixed with other ingredients such as fish oil, grain, counterbalancing ingredients, special purpose additives (eg, vitamin and mineral mixtures, mineral salts, cellulose And sugar beet pulp, filler, and the like) and water in an amount sufficient for processing. These ingredients are mixed in a container suitable for heating during mixing of the components. Heating of the mixture is accomplished using any suitable method, such as direct steam injection or using a vessel equipped with a heat exchanger. After the addition of the last component, the mixture is heated to a temperature of about 50 ° F. to about 212 ° F. Temperatures outside this range are acceptable, but may not be commercially practical without the use of other processing aids. When heated to the appropriate temperature, the material will typically be in the form of a thick liquid. Fill the can with the concentrated liquid. Install the lid and seal the container tightly. The sealed can is then placed in a commonly used facility designed to sterilize the contents. Sterilization is usually achieved by heating to temperatures above about 230 ° F. for an appropriate time depending on the temperature, composition, and similar factors used. The compositions of the present invention can be added to the food composition before, during, or after preparation.

  [0066] The food composition may be prepared in dry form using commonly used processes known to those skilled in the art. Typically, dry ingredients such as animal protein, vegetable protein, cereal, and the like are ground and mixed together. The wet or liquid ingredients including fat, oil, animal protein, water, and the like are then added to and mixed with the dry mixture. The mixture is then processed into kibbles or similar dry pieces. Kibbles are often formed using an extrusion process in which a mixture of dry and wet ingredients is subjected to mechanical work at high pressure and temperature, pushed through a small opening and cut off with a rotating knife to kibble. The wet kibble is then dried and optionally coated with one or more topical coatings such as flavors, fats, oils, powders, and the like. Kibbles can also be made from a dough that has been baked using a baking process rather than extrusion, where the kneaded dough is placed in a mold and then dried-heated. The food composition is an extrusion or baking process similar to the process described above for dry hoods or toys, such as the processes disclosed in US Pat. Nos. 5,339,771 and 5,419,283. It can also be in the form of treats using. The compositions of the present invention can be added to the food composition before, during, or after preparation.

Method of the present invention
[0067] The present invention also includes a method for improving liver function in an animal. The method includes providing an animal in need thereof with an amount of lipoic acid or a salt thereof effective to improve liver function. Generally, the lipoic acid is given to the animal in an amount of 25 ppm to 2600 ppm. In certain illustrative aspects, the amount can vary from 25 ppm to 2600 ppm or to an amount that remains non-toxic to the pet. In other embodiments, the range is 50 ppm to 1200 ppm. In other embodiments, the range is 65 ppm to 650 ppm.

  [0068] The present invention also includes a method for improving immune function in an animal. The method includes providing an animal in need thereof with an amount of lipoic acid or a salt thereof effective to improve immune function. Generally, the lipoic acid is given to the animal in an amount of 25 ppm to 2600 ppm. In certain illustrative aspects, the amount can vary from 25 ppm to 2600 ppm or to an amount that remains non-toxic to the pet. In other embodiments, the range is 50 ppm to 1200 ppm. In other embodiments, the range is 65 ppm to 650 ppm.

  [0069] The method of the present invention is used to improve the liver function or immune function in an animal, such as a companion animal, such as a feline, especially when these functions may be impaired by age and To provide a composition or feed comprising lipoic acid or a salt thereof to improve the overall health of the animal. The amount of lipoic acid given to the animal is a non-toxic amount. The lipoic acid may be provided as a supplement to the animal, or may be included in a composition comprising a feed provided to the animal. Such supplements may be in the form of pills or capsules, treats or biscuits, or any other edible form. By “feed” is meant food or beverage that is consumed regularly by the animal. The feed may contain supplements consumed by the animal. The feed is considered to have essentially enough nutrients to maintain life for the animal. The companion animal feed can be any suitable pet food formula, which also provides sufficient nutrition for the animal. For example, a typical feline feed suitable for use in the present invention comprises 8 to 50% fat, 16 to 50% by weight protein, and 3 to 15% total dietary fiber. May be. In another example, a typical feline feed may contain 8 to 50% by weight fat and 30 to 60% by weight protein. However, specific ratios or percentages of these or other nutrients are not required. Nutrients are every food component that helps support life. Nutrients important to animal health are known to those skilled in the art, such as proteins, carbohydrates, fats, fiber, vitamins, and minerals. Water is also essential for animal health.

  [0070] Various aspects of the invention include methods for improving liver or immune function in animals, particularly companion animals. In such embodiments, the method includes providing the animal with a composition, eg, feed, comprising lipoic acid or a salt thereof in an amount of at least 25 ppm on a dry matter basis. In yet another embodiment, the method includes providing the animal with a feed comprising lipoic acid in an amount from 65 ppm to 650 ppm on a dry matter basis. As used herein, lipoic acid is a racemic mixture, but other embodiments are essentially pure R-α lipoic acid, or lipoate derivatives, mixtures of isomers, salts, esters, amides. Or lipoic acid as a combination thereof (see, for example, US Pat. No. 5,621,177 issued to Bethge et al., Issued April 15, 1997). In various embodiments, the range of lipoic acid that can be administered to a cat is from 25 ppm to 2600 ppm. In certain illustrative aspects, the amount can vary from 65 ppm to 2600 ppm or to an amount that remains non-toxic to the pet. In other embodiments, the range is from 50 ppm to 1200 ppm. In other embodiments, the range is from 65 ppm to 650 ppm.

  [0071] In various embodiments, the composition or feed comprises at least 25 ppm to 2600 ppm lipoic acid or salt thereof. In some embodiments, the lipoic acid or salt thereof is added to a companion animal food. In such embodiments, the lipoic acid or salt thereof may be added during processing of the companion animal food, which is then packaged and made available to the consumer. Such processing may include extrusion, canning, baking, and the like, or any other method or process for producing a pet food known in the art. In such processing, the lipoic acid may be contributed by a natural source such as an animal or plant component, e.g. kidney or spinach, or the lipoic acid may be contributed by a source derived from synthesis or the lipoic acid. The acid may be contributed by a mixture of natural and synthetic sources. In other embodiments, the lipoic acid may be in the form of a capsule provided to the companion animal. In yet other embodiments, the lipoic acid or salt thereof may be powdered or crystalline, which may be added to the animal's food or given directly to the animal. In various embodiments, the companion animal feed comprises lipoic acid or a salt thereof and other required nutritional components. In various embodiments, the companion animal is a dog, and in other embodiments, the companion animal is a cat.

  [0072] In a further aspect, the present invention provides the use of lipoic acid or a salt thereof for the preparation of a medicament. In another aspect, the present invention provides an animal with an amount of lipoic acid or a salt thereof to maintain and / or improve the health of the animal, for example to improve liver function or immune function in the animal The use of lipoic acid for the preparation of a medicament is provided. In general, pharmaceuticals are suitable for administration of compounds or compositions to animals, excipients, buffers, binders, plasticizers, colorants, diluents, compression agents, lubricants, flavoring agents, wetting agents, as well as those skilled in the art. Prepared by mixing with other ingredients known to be useful in formulating pharmaceuticals and formulating pharmaceuticals.

  [0073] In a further aspect, the present invention provides a kit suitable for providing an animal with lipoic acid or a salt thereof. The kit includes lipoic acid and at least one of the following, as appropriate, in separate containers in a single package or in separate containers in a virtual package: (1) One or more components suitable for consumption by animals, (2) to produce a composition useful for improving liver clearance of xenobiotics, particularly useful for improving liver clearance of xenobiotics, and Instructions on how to combine the components of other kits, and (3) instructions on how to use the lipoic acid and other components of the invention, especially for animal benefit. Where the kit includes a virtual package, the kit is limited to instructions in a virtual environment in combination with one or more physical kit components. The kit contains lipoic acid and other components in an amount sufficient to improve liver clearance of xenobiotics. Typically, the lipoic acid and other suitable kit components are mixed immediately prior to consumption by the animal. In one embodiment, the kit includes a small packet containing lipoic acid and a food container for consumption by animals. The kit may include additional items such as a tool for mixing lipoic acid and ingredients or a tool for containing the mixture, such as a food ball. In another embodiment, lipoic acid is mixed with additional nutritional supplements that promote good health in animals, such as vitamins and minerals.

  [0074] The invention is not limited to the particular methodologies, protocols, and reagents described herein, as they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention. As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. The terms “comprise”, “comprises”, and “including” are to be interpreted inclusively rather than exclusively.

  [0075] Unless defined otherwise, all technical and scientific terms used herein and all acronyms have the same meaning as commonly understood by one of ordinary skill in the art in the field of the invention. . Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods, tools, and materials are described herein. .

  [0076] All patents, patent applications, and publications referred to herein are reported in their compositions, compounds, methods, and similar information that may be used with the present invention. Is hereby incorporated by reference to the extent permitted by law. However, nothing in this specification should be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.

  [0077] This invention can be further illustrated by the following examples of preferred embodiments thereof, which are included for illustrative purposes only, and unless otherwise clearly indicated. It will be understood that it is not intended to limit the scope.

Example 1
[0078] The study included three groups of cats: group 1) cats eating dry control food, group 2) cats eating dry food enriched with approximately 65 ppm lipoic acid on a dry matter basis, and group 3 ) Cat eating dry food enriched with approximately 650 ppm lipoic acid. All cats were given a control food for a 2-week baseline period, at which time the immune function assay was performed. Then one cat group was switched to the 65 ppm test hood, one group was switched to the 650 ppm test hood, one group was left as a control and all groups were given for another 6 weeks, at which point the baseline test was performed again. It was.

  [0079] Administration of lipoic acid to older cats improves lymphocyte proliferative activity, which may improve immune function. The effect on improving lymphocyte proliferation in healthy cats at a single level of lipoic acid content (eg 65 ppm) was most prominent.

  [0080] As illustrated in FIG. 1, inclusion of lipoic acid in feline pet food at 65 ppm and 650 ppm had no adverse effect on body weight with respect to cats.

  [0081] FIG. 2 illustrates the effects of 65 ppm and 650 ppm content in feed and time points on concanavalin A stimulation. There were no significant differences between the groups at the start of the study or at the end of the study. However, cats containing 65 ppm lipoic acid significantly increased the proliferation of lymphocytes activated by concanavalin A compared to baseline. Cats at 650 ppm also showed an increase. Thus, based on the proliferation of lymphocytes activated by concanavalin A, the addition of 65 ppm or 650 ppm lipoic acid to the cat food composition could increase the cat's immune response.

  [0082] FIG. 3 illustrates that plant agglutinin (PHA) stimulation did not show significant differences between groups at the start or end. The explanatory group receiving 65 ppm lipoic acid had a significant increase in lymphocyte proliferation between baseline and 6 weeks of intervention. Thus, based on the proliferation of lymphocytes activated by PHA, the addition of 65 ppm or 650 ppm lipoic acid to the cat food composition could increase the cat's immune response.

  [0083] FIG. 4 illustrates that American pokeweed mitogen stimulation was different between groups at the start of the study (ANOVA P <0.05) but not at the end. The group with the lowest starting average was the 65 ppm group. Subsequently, lymphocyte proliferation in the group receiving 65 ppm lipoic acid increased significantly compared to baseline after a time of 6 weeks. Thus, based on the proliferation of lymphocytes activated by American pokeweed mitogen, the addition of 65 ppm or 650 ppm lipoic acid to the cat food composition could increase the cat's immune response.

  [0084] Figures 5a and 5b illustrate the activity of natural killer cells. Based on an illustrative test, no significant change was detected from baseline to the end of the test for a 10: 1 stimulation ratio; however, all p values were less than 0.1. At a stimulation ratio of 50: 1, all changes between baseline and end of study were significant for all groups.

  [0085] FIG. 6 illustrates a graph for a representative comet assay. Two illustrative assays were performed: (1) natural DNA damage and (2) damage loaded with hydrogen peroxide. Analysis of the data showed that all head DNA for all feeds increased significantly over the duration of the test for both (P <0.05). In addition, the tail length and olive tail moments of all tail DNAs decreased during the duration of the test for both the control and the hydrogen peroxide-loaded comet test. However, there was no significant difference between groups at either start or end for any of the comet measurements. In addition, ANOVA analysis of changes over time (pre-post-difference) showed no significant difference by t-test for each comet variation under control and hydrogen peroxide loading conditions.

  [0086] In the specification, typical preferred embodiments of the invention have been disclosed and specific terms have been used, but are used in a generic and descriptive sense only and not for purposes of limitation. The scope of the invention is set forth in the following claims. Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims, the invention may be practiced otherwise than as specifically described.

Claims (25)

A composition comprising an amount of lipoic acid or a salt thereof effective to improve liver or immune function in an animal, wherein the amount of lipoic acid effective to improve liver or immune function in said animal is at least about A composition that is 25 ppm. The composition of claim 1 wherein the effective amount is 25 ppm to 2600 ppm lipoic acid or salt thereof. The composition of claim 1, wherein the effective amount is 50 ppm to 1200 ppm lipoic acid or salt thereof. The composition of claim 1, wherein the effective amount is from 65 ppm to 650 ppm lipoic acid or a salt thereof. The composition of claim 1, wherein the animal is a companion animal. 6. The composition of claim 5, wherein the companion animal is a feline animal. The composition of claim 1, wherein the composition is a food composition. 8. The composition of claim 7, wherein the food composition is a dry food composition. The composition according to claim 7, wherein the food composition is extruded. 8. A composition according to claim 7, wherein the food composition is canned. A method for improving liver or immune function in an animal in need thereof, comprising providing said animal with an effective amount of lipoic acid or a salt thereof, said effective amount improving liver or immune function A way that is effective. 12. The method of claim 11, wherein the effective amount is 25 ppm to 2600 ppm lipoic acid or salt thereof. 12. The method of claim 11, wherein the effective amount is 50 ppm to 1200 ppm lipoic acid or salt thereof. 12. The method of claim 11, wherein the effective amount is from 65 ppm to 650 ppm lipoic acid or salt thereof. 12. The method of claim 11, wherein the animal is a companion animal. The method of claim 15, wherein the companion animal is a feline. 2. The method of claim 1, wherein the lipoic acid or salt thereof is part of the animal's daily diet. 18. The method of claim 17, wherein the daily feed comprises an amount of lipoic acid or salt thereof greater than 25 ppm based on dry weight. 12. The method of claim 11, wherein the lipoic acid or salt thereof is in a dry food composition. 12. The method of claim 11, wherein the animal is an elderly animal. A composition suitable for improving immune function in an animal comprising the following: an amount of nutrients; and greater than 25 ppm lipoic acid or salt thereof. 24. The composition of claim 21, wherein the composition is a food composition. The composition of claim 21, wherein the food composition is suitable for a companion animal. 24. The composition of claim 21, wherein the food composition is suitable for a feline. 24. The composition of claim 21, wherein the composition is extruded or canned.

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